Current Drug Targets and Future Therapy of Pulmonary Arterial Hypertension

Author(s): Takayuki Ito, Keiya Ozawa, Kazuyuki Shimada.

Journal Name: Current Medicinal Chemistry

Volume 14 , Issue 6 , 2007

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Abstract:

During the last few decades, we have witnessed major improvements in the therapy of pulmonary arterial hypertension (PAH). PAH is characterized by abnormal remodeling of the pulmonary artery (PA) and increased PA pressures, resulting in a high premature mortality. Intravenous epoprostenol was the first effective approach toward improving the symptoms and survival of PAH patients. New prostanoids have also exhibited substantial clinical benefits; however, their long-term effects are under investigation. Endothelin-receptor antagonists and sildenafil have increased the lineup of therapeutic options against PAH. Combination therapy using these drugs is promising and is currently undergoing scrutiny in large clinical trials. An extensive analysis of the molecular mechanisms of PAH will produce novel targeted therapies. Most of the promising molecules target the inflammatory and proliferative processes underlying pathological PA remodeling. Interestingly, drugs used for other diseases, such as statins, Rho-kinase inhibitors, imatinib mesylate, may control the pathological vascular remodeling of PAH. Gene and cell therapy using vectors expressing prostacyclin synthase, endothelial nitric oxide synthase, or vascular endothelial growth factor are also promising strategies. However, the efficacy and safety of these approaches should be further tested in clinical trials. Genetic studies revealed some crucial genetic dispositions of familial PAH, although their pathobiological roles have not yet been fully clarified. Collaboration for integrated research will address these issues and generate greater clinical benefits for PAH patients.

Keywords: Pulmonary arterial hypertension, treatment, prostacyclin, endothelin, sildenafil, gene therapy, inflammation, proliferation

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Article Details

VOLUME: 14
ISSUE: 6
Year: 2007
Page: [719 - 733]
Pages: 15
DOI: 10.2174/092986707780059562
Price: $58

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